Interaction between interleukin-1 and ciliary neurotrophic factor in the regulation of neuroblastoma cell functions.
Human neuroblastoma cells SK-N-SH express significant numbers of IL-1R type I on their surface, as detected by saturation binding and RT-PCR, and are responsive to IL-1beta activation by producing inflammatory cytokines IL-6 and IL-8. IL-1beta can also have an indirect effect on nervous cell functions, since it is able to modulate the stimulus-induced increase of intracellular Ca++ levels, one of the first steps of the cell activation mechanism. In fact, on SK-N-SH neuroblastoma cells, IL-1beta can inhibit the Ca++ increase induced by stimulation of acetylcholine receptors with carbachol. In parallel to IL-1beta, the neurotrophic factor CNTF also shows an inhibitory effect on carbachol-stimulated Ca++ increase in CNTFRalpha-expressing SK-N-SH cells. However, when simultaneously present, the two cytokines cross-inhibit, thus allowing full cell activation in response to the cholinoceptor agonist. The inhibitory effect of CNTF on IL-1beta activities on nervous cells was confirmed in the IL-6 production assay. In fact, while CNTF could not induce IL-6 production, it could strongly inhibit cytokine production in response to IL-1beta in SK-N-SH cells. The down-modulation of IL-1 effects by CNTF could be one of the mechanisms controlling the extent of the inflammatory reaction at the nervous system level.
Bossù
P
P
Research Center Dompé SpA, L'Aquila, Italy.
Ruggiero
P
P
Macchia
G
G
Maurizi
G
G
Bizzarri
C
C
Neumann
D
D
Tagliabue
A
A
Boraschi
D
D
D020934:Ciliary Neurotrophic Factor; D015536:Down-Regulation; D006801:Humans; D007249:Inflammation / Q000378:metabolism*; D007375:Interleukin-1 / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D009447:Neuroblastoma / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism*; D016133:Polymerase Chain Reaction / Q000379:methods; D017472:Receptors, Interleukin-1 / Q000096:biosynthesis; D014158:Transcription, Genetic
D020934:Ciliary Neurotrophic Factor; D007375:Interleukin-1; D009419:Nerve Tissue Proteins; D017472:Receptors, Interleukin-1